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Updated: Feb 19, 2026

Metabolic Glycoengineering of Sialic Acid Using N-acyl-modified Mannosamines
Published on: November 25, 2017
Discovery of a Small-Molecule Modulator of Glycosaminoglycan Sulfation
Sheldon T Cheung1, Michelle S Miller1, Reynand Pacoma2
1Division of Chemistry and Chemical Engineering, California Institute of Technology , 1200 East California Boulevard, Pasadena, California 91125, United States.
Abstract:
Glycosaminoglycans (GAGs) play critical roles in diverse processes ranging from viral infection to neuroregeneration. Their regiospecific sulfation patterns, which are generated by sulfotransferases, are key structural determinants that underlie their biological activity. Small-molecule modulators of these sulfotransferases could serve as powerful tools for understanding the physiological functions of GAGs, as well as potential therapeutic leads for human diseases. Here, we report the development of the first cell-permeable, small-molecule inhibitor selective for GAG sulfotransferases, which was obtained using a high-throughput screen targeted against Chst15, the sulfotransferase responsible for biosynthesis of chondroitin sulfate-E (CS-E). We demonstrate that the molecule specifically inhibits GAG sulfotransferases in vitro, decreases CS-E and overall sulfation levels on cell-surface and secreted chondroitin sulfate proteoglycans (CSPGs), and reverses CSPG-mediated inhibition of axonal growth. These studies pave the way toward a new set of pharmacological tools for interrogating GAG sulfation-dependent processes and may represent a novel therapeutic approach for neuroregeneration.
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